DESCRIPTION: (Adapted from the author's abstract.) Currently, more than one million Americans are believed to be infection with HIV-1. Fifty to eighty percent of individuals with HIV-1 infection experience significant visual loss prior to death, further complicating an already devastating disease process. Coinfection of the human retina with HIV-1 and human herpesviruses--documented by other investigators--may have important implications with regard to pathogenic mechanisms of retinitis associated with AIDS. The researchers' current work suggests that interactions between HIV-1 and human herpesvirus, Type 6 (HHV-6)--a recently-described human herpesvirus that has been isolated from peripheral blood leukocytes of patients with AIDS and other disorders of an immunoproliferative nature- -may result in activation of one or both viruses.Whereas several human herpesviruses have been shown to transactivate HIV-1 in vitro, HHV-6 is the only herpesvirus that shares cell tropism with HIV-1 and is able to coinfect productively CD4+ lymphocytes leading to an accelerated cytopathic effect when compared to HIV-1 infection alone. The proposed project is an extension of the ongoing research, the overall purpose of which is to study the agents and mechanisms involved in the development of AIDS-associated retinitis and to determine whether corneal and retinal cells are capable of supporting active HIV-1 infection. The researchers will address (1) the frequency and proximity of simultaneous occurrence of HIV-1, HHV-6, and CMV in retinal lesions and the identity of infected cell types, (2) the effect of coinfection of retinal and corneal cells with HIV-1 and HHV-6, and (3) the cell tropism of corneal and retinal HIV-1 isolates and the HIV-1 genomic region(s) responsible for cell tropism. The Investigator believes that some, if not all, of these factors may be involved in the development of AIDS-associated retinitis.